Differential vasomotor action of noradrenaline, serotonin, and histamine in isolated basilar artery from rat and guinea‐pig

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Abstract
Vasomotor effects of the amines, serotonin (5‐hydroxytryptamine; 5‐HT), noradrenaline (NA) and histamine, were studied in isolated basilar arteries (BA) of the rat and guinea‐pigin vitro.5‐HT produced marked contraction in rat BA, about 70% of that induced by high (124 mM) K+solution. This response was inhibited by the specific 5‐HT2receptor antagonist, ketanserin, with a pA2value of 9.35. In the guinea‐pig, 5‐HT caused only moderate contraction amounting to 30% of that produced by K+. Ketanserin at concentrations up to 10‐6M showed a comparatively small, non‐surmountable inhibition of the contraction.EC50values for 5‐HT in the guinea‐pig and rat were 5.65 times 10‐8m and 3.70 times 10‐7M, respectively. NA had no effect on rat BA, but moderately contracted guinea‐pig BA. The contraction was not altered by yohimbine but was inhibited by prazosin. Histamine contracted guinea‐pig BA with a maximum that was 110% of the K+‐induced contraction. It was not changed by the H2antagonist, cimetidine. The H1antagonist, pyrilamine, caused competitive inhibition with a pA2of 9.20 at a slope of 0.94. In preconstricted rat BA, histamine induced vasodilatation in a concentration‐dependent manner. The Hj agonist, pyridylethylamine (PEA), and the H2agonist, impromidine, dilated less effectively than histamine. The vasodilatation induced by histamine was inhibited by the H2antagonist, cimetidine, and to a smaller extent by the H1‐receptor antagonist, pyrilamine. Removal of the endothelium abolished the vasodilator effect of PEA but not that of impromidine. In vessels with intact endothelium, the vasodilatation caused by histamine was slightly reversed by pyrilamine, which did not affect the dilatation in endothelium denuded vessels. Cimetidine markedly reversed this vasodilator effect in both intact and endothelium denuded preparations; in the latter the counteraction was almost complete. In precontracted guinea‐pig vessels, histamine failed to induce dilatation even in the presence of the H1antagonist, pyrilamine. Thus, 5‐HT‐induced contraction is mediated by 5‐HT2receptors in the rat and probably by 5‐HT1receptors in the guinea pig. NA failed to contract rat BA but contracted guinea‐pig BA through α1receptors. Histamine was a potent dilator agent in rat BA through a combination of both H1and H2receptors. The dilatation mediated by the H1receptors, but not that mediated by H2receptors, was endothelium‐dependent. Histamine caused strong vasoconstriction in the guinea‐pig BA through H1receptors.